Objectives
Lipid mediators are bioactive lipids which help regulate inflammation. We aimed to develop an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify 58 pro-inflammatory and pro-resolving lipid mediators in plasma, determine preliminary reference ranges for adolescents, and investigate how total parenteral nutrition (TPN) containing omega-3 polyunsaturated fatty acid (n-3 PUFA) or n-6 PUFA based lipid emulsions influence lipid mediator concentrations in plasma.
Methods
Lipid mediators were extracted from plasma using SPE and measured using UHPLC-MS/MS. EDTA plasma was collected from healthy adolescents between 13 and 17 years of age to determine preliminary reference ranges and from mice given intravenous TPN for seven days containing either an n-3 PUFA or n-6 PUFA based lipid emulsion.
Results
We successfully quantified 43 lipid mediators in human plasma with good precision and recovery including several leukotrienes, prostaglandins, resolvins, protectins, maresins, and lipoxins. We found that the addition of methanol to human plasma after blood separation reduces post blood draw increases in 12-hydroxyeicosatetraenoic acid (12-HETE), 12-hydroxyeicosapentaenoic acid (12-HEPE), 12S-hydroxyeicosatrienoic acid (12S-HETrE), 14-hydroxydocosahexaenoic acid (14-HDHA) and thromboxane B2 (TXB2). Compared to the n-6 PUFA based TPN, the n-3 PUFA based TPN increased specialized pro-resolving mediators such as maresin 1 (MaR1), MaR2, protectin D1 (PD1), PDX, and resolvin D5 (RvD5), and decreased inflammatory lipid mediators such as leukotriene B4 (LTB4) and prostaglandin D2 (PGD2).
Conclusions
Our method provides an accurate and sensitive quantification of 58 lipid mediators from plasma samples, which we used to establish a preliminary reference range for lipid mediators in plasma samples of adolescents; and to show that n-3 PUFA, compared to n-6 PUFA rich TPN, leads to a less inflammatory lipid mediator profile in mice.
Despite a global increase in childhood obesity over the past decades, several countries, including Switzerland, have recently reported stabilizing trends. Using national data from school-aged children in Switzerland over the past 16 years, our study aim was to assess changes in the prevalence of overweight and obesity, central adiposity and predictors of obesity related to lifestyle and parental factors. Nationally representative samples of children aged 6–12 years were studied in 2002 (n = 2493), 2007 (n = 2218), 2012 (n = 2963), and 2017/18 (n = 2279). Height and weight, waist circumference, and multiple skinfold thicknesses were measured. Potential risk factors for overweight and obesity were determined using a self-administered questionnaire in 2017/18, collecting data on diet, physical activity, and parental factors. Prevalence (95% CI) of overweight (incl. obesity) and obesity in 2017/18 was 15.9% (14.4–17.4) and 5.3% (4.5–6.3), respectively. Binary logistic regression revealed a small but significant decrease in the prevalence of overweight (including obesity) since 2002 (OR (95% CI) = 0.988 (0.978–0.997)), while the change in obesity alone was not significant. The most important risk factors for childhood overweight/obesity in 2017/18 were low parental education, non-Swiss origin of the parents, low physical activity of the child, and male sex. In conclusion, we have shown a small but significant declining trend in the childhood overweight/obesity prevalence over the past 15 years in Switzerland. Based on the risk factor analysis, preventive action in schoolchildren might be most effective in boys, migrant populations, and families with lower education, and should emphasize physical activity.
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